The goal of this proposed research is to define the molecular structures that determine the antigenetic reactivity of the human Rh system. Using pre-existing human monoclonal antibodies directed against a large G determinant and one directed against a determinant found on Rh D+ cells but no Du cells, we will refine the characterization of the human Rh system. In addition to the above antibodies we will make more antibodies directed against determinants of the Rh system. This will be done using a human myeloma fusion partner to immortalize sensitized lymphocytes obtained from Rh immune donors. The genes for these antibodies will then be manipulated by a variety of DNA cloning techniques to increase the affinity and to switch the isotypes. After successful completion of the first phase of this work we will extend the work to provide a commercial supply of human monoclonal anti-Rh reagents for blood typing and for therapy of hemolytic disease of the newborn and autoimmune hemolytic anemia.